Summary of the safety profile The most frequently reported adverse reactions considered possibly or probably related to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Gilead in clinical studies through 144 weeks in treatment-naïve adult patients were nausea (16%) and diarrhoea (12%).
The most frequently reported adverse reactions to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Gilead in clinical studies through 48 weeks in virologically-suppressed adult patients were nausea (3% to 5%) and fatigue (6%).
In patients receiving tenofovir disoproxil, rare events of renal impairment, renal failure and uncommon events of proximal renal tubulopathy (including Fanconi syndrome) sometimes leading to bone abnormalities (infrequently contributing to fractures) have been reported.
4). 4). Tabulated summary of adverse reactions Adverse reactions to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Gilead from Phase 3 clinical studies GS-US-236-0102 and GS-US-236-0103 and adverse reactions to treatment with emtricitabine and tenofovir disoproxil from clinical studies and post-marketing experience, when used with other antiretrovirals, are listed in Table 2, below, by body system organ class and highest frequency observed.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100) or rare (≥ 1/10,000 to < 1/1,000).
Table 2:
Tabulated summary of adverse reactions associated with Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Gilead based on experience from Phase 3 studies GS-US-236-0102 and GS-US-236-0103 and adverse reactions to treatment with emtricitabine and tenofovir disoproxil from clinical studies and post-marketing experience, when used with other antiretrovirals Frequency Adverse reaction Blood and lymphatic system disorders: Common: neutropenia1 Uncommon: anaemia1,2 Immune system disorders: Common: allergic reaction1 Metabolism and nutrition disorders: Very common: hypophosphataemia1,3 Common: hyperglycaemia1, hypertriglyceridaemia1, decreased appetite Uncommon: hypokalaemia1,3 Rare: lactic acidosis1 Psychiatric disorders: Common: insomnia, abnormal dreams Uncommon: suicidal ideation and suicide attempt (in patients with a pre- existing history of depression or psychiatric illness), depression Frequency Adverse reaction Nervous system disorders: Very common: headache, dizziness Gastrointestinal disorders: Very common: diarrhoea, vomiting, nausea Common: elevated amylase including elevated pancreatic amylase1, elevated serum lipase1, abdominal pain, dyspepsia, constipation, abdominal distension1, flatulence Uncommon: pancreatitis1 Hepatobiliary disorders: Common: increased transaminases1, hyperbilirubinaemia1 Rare: hepatic steatosis1, hepatitis1 Skin and subcutaneous tissue disorders: Very common: rash Common: vesiculobullous rash1, pustular rash1, maculopapular rash1, pruritus1, urticaria1, skin discolouration (increased pigmentation)1,2 Uncommon: angioedema1 Musculoskeletal and connective tissue disorders: Very common: elevated creatine kinase1 Common: bone mineral density decreased Uncommon: rhabdomyolysis1,3, muscular weakness1,3 Rare: osteomalacia (manifested as bone pain and infrequently contributing to fractures)1,3,5, myopathy1,3 Renal and urinary disorders: Common: increased blood creatinine4 Uncommon: renal failure4, proximal renal tubulopathy including Fanconi syndrome acquired4, proteinuria Rare: acute tubular necrosis1, nephritis (including acute interstitial nephritis)1,5, nephrogenic diabetes insipidus1 General disorders and administration site conditions: Very common: asthenia1 Common: pain1, fatigue 1 This adverse reaction was not observed in the Phase 3 clinical studies for Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Gilead but identified from clinical studies or post-marketing experience for emtricitabine or tenofovir disoproxil when used with other antiretrovirals.
2 Anaemia was common and skin discolouration (increased pigmentation) was very common when emtricitabine was administered to paediatric patients. 3 This adverse reaction may occur as a consequence of proximal renal tubulopathy. It is not considered to be causally associated with tenofovir disoproxil in the absence of this condition.
8, Description of selected adverse reactions for more details. 5 This adverse reaction was identified through post-marketing surveillance for emtricitabine or tenofovir disoproxil but not observed in randomised, controlled clinical studies in adults or paediatric HIV clinical studies for emtricitabine or in randomised controlled clinical studies or the tenofovir disoproxil expanded access program for tenofovir disoproxil.
The frequency category was estimated from a statistical calculation based on the total number of patients exposed to emtricitabine in randomised controlled clinical studies (n = 1,563) or tenofovir disoproxil in randomised controlled clinical studies and the expanded access program (n = 7,319).
Description of selected adverse reactions Renal impairment Proximal renal tubulopathy generally resolved or improved after tenofovir disoproxil discontinuation. However, in some patients, declines in creatinine clearance did not completely resolve despite tenofovir disoproxil discontinuation.
Patients at risk of renal impairment (such as patients with baseline renal risk factors, advanced HIV disease, or patients receiving concomitant nephrotoxic medications) are at increased risk of experiencing […]